A prominent feature of mammalian visual cortex is that it is composed of many different areas which are linked through reciprocal connections. Forward connections mediate the flow of information from peripheral to more central areas, whereas feedback projections convey information from higher to lower areas. The feedback projections that are of interest here are those that connect higher cortical areas with primary visual cortex. Such projections may have access to both intracortical and subcortical projection systems, on which they may exert different influences. The role of feedback input to corticocortically projecting neurons may be to modify receptive field properties of striate cortical neurons based on information extracted in functionally different cortical areas, and to provide for a coherent representation of a visual stimulus at an early stage in the cortical hierarchy. By contrast, the role of feedback input to subcortical projection systems, may be to select specific afferent information or to direct attention to a particular point of the visual field. The underlying hypothesis is that these different functions are implemented by different circuits. Because it is likely that each of the efferent projections systems, including local interneurons, receive feedback input the difference in the organization may lie in the strength, and the subcellular distribution of inputs. This organization may in part determine the timecourse and amplitude of monosynaptic potentials that activate different cell types. In addition, differences in postsynaptic responses may also arise from the activation of different transmitter receptors that are known to be preferentially distributed in different layers, and possibly also in neurons that give rise to different projections. Thus, the goal of the proposed project is to determine the strength and subcellular distribution of feedback input from higher cortical areas to interneurons and different types of projection neurons in primary visual cortex, and to determine the mechanism(s) that underlay feedback activation of these cell types. To achieve this goal, we will determine, using anterograde neuronal tracing and a combination of light- (LM) and electron microscopic (EM) analyses, the laminar distribution and relative strength of feedback projections from secondary to primary visual cortex in rat (aim 1). To determine feedback input to GABAergic interneurons of neuronal tracing and immunocytochemistry will be used to identify synaptic contacts under the LM and EM (aim 2). Anterograde and retrograde tracing and correlative LM and EM analyses will be employed to determine feedback input to striate cortical cells that project to secondary visual cortex (aim 3). A similar approach will be used to determine feedback input to colliculus projecting neurons (aim 4). Using intracellular recordings in in vitro slices we will examine whether activation of feedback input elicits different types of monosynaptic EPSPs in different cell types (aim 5). To examine whether the postsynaptic responses in different cells are mediated by different receptors we will use intracellular recordings and selective antagonists of different excitatory amino acid receptors (aim 6).